紧密连接蛋白claudin 18.2(CLDN18.2)在胃癌和胰腺癌等恶性肿瘤中异常高表达,基于其高组织特异性、广泛患者覆盖性及多技术路径开发潜力,成为癌症治疗领域备受关注的新靶点。近年来,针对CLDN18.2的创新药物研发取得显著突破,尤其是首个...紧密连接蛋白claudin 18.2(CLDN18.2)在胃癌和胰腺癌等恶性肿瘤中异常高表达,基于其高组织特异性、广泛患者覆盖性及多技术路径开发潜力,成为癌症治疗领域备受关注的新靶点。近年来,针对CLDN18.2的创新药物研发取得显著突破,尤其是首个靶向CLDN18.2的抗体药物zolbetuximab于2024年在日本获批上市,标志着CLDN18.2靶向治疗进入新阶段。综述CLDN18.2作为肿瘤治疗靶点的生物学基础,重点介绍针对该靶点的抗体药物、抗体药物偶联物(antibody drug conjugate,ADC)、嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)疗法及放射性核素偶联药物(radionuclide drug conjugate,RDC)等治疗策略的研究进展,旨在为CLDN18.2靶向药物进一步研发与临床应用提供参考。展开更多
Objective:This study examines the significance and functions of CLDN9 in gastric cancer(GC),intending to identify novel targets for diagnosis and treatment.Methods:CLDN9 expression in GC tissues and cell lines was inv...Objective:This study examines the significance and functions of CLDN9 in gastric cancer(GC),intending to identify novel targets for diagnosis and treatment.Methods:CLDN9 expression in GC tissues and cell lines was investigated in TCGA data,with analysis with Western blotting,qRT-PCR,and immunohistochemical analyses.Correlations between clinicopathological characteristics,progression-free survival(PFS),and overall survival(OS)were assessed with Cox regression.The effect of CLDN9 knockdown/overexpression on tumorigenic functions(proliferation,migration,and invasion)was assessed using CCK-8,colony formation,and Transwell assays.Tumor-bearing assays were performed to verify the impact of CLDN9 knockdown on the in vivo proliferation of GC cells.Results:Analysis of TCGA data,qRT-PCR,Western blotting,and immunohistochemistry indicated significantly elevated levels of CLDN9 in GC tissues and cell lines(p 0.01).Compared to the group with high CLDN9 expression,<PFS and OS were markedly longer in cases with low CLDN9 levels(p 0.05).Multivariate regression indicated that<CLDN9 levels were independently predictive of GC prognosis.CCK-8,Transwell,and colony formation tests showed that CLDN9 overexpression promoted GC cell proliferation,clonogenicity,and migratory/invasive capabilities,but CLDN9 knockdown markedly reduced these features.Experiments involving tumor-bearing models demonstrated that the suppression of CLDN9 inhibited the in vivo growth of GC cells.Conclusion:In conclusion,this study’s findings suggested that CLDN9 might be a valuable therapeutic target or diagnostic biomarker for GC.展开更多
文摘紧密连接蛋白claudin 18.2(CLDN18.2)在胃癌和胰腺癌等恶性肿瘤中异常高表达,基于其高组织特异性、广泛患者覆盖性及多技术路径开发潜力,成为癌症治疗领域备受关注的新靶点。近年来,针对CLDN18.2的创新药物研发取得显著突破,尤其是首个靶向CLDN18.2的抗体药物zolbetuximab于2024年在日本获批上市,标志着CLDN18.2靶向治疗进入新阶段。综述CLDN18.2作为肿瘤治疗靶点的生物学基础,重点介绍针对该靶点的抗体药物、抗体药物偶联物(antibody drug conjugate,ADC)、嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)疗法及放射性核素偶联药物(radionuclide drug conjugate,RDC)等治疗策略的研究进展,旨在为CLDN18.2靶向药物进一步研发与临床应用提供参考。
基金supported by the Science and Technology Plan of Suqian City(Grant No.S202117).
文摘Objective:This study examines the significance and functions of CLDN9 in gastric cancer(GC),intending to identify novel targets for diagnosis and treatment.Methods:CLDN9 expression in GC tissues and cell lines was investigated in TCGA data,with analysis with Western blotting,qRT-PCR,and immunohistochemical analyses.Correlations between clinicopathological characteristics,progression-free survival(PFS),and overall survival(OS)were assessed with Cox regression.The effect of CLDN9 knockdown/overexpression on tumorigenic functions(proliferation,migration,and invasion)was assessed using CCK-8,colony formation,and Transwell assays.Tumor-bearing assays were performed to verify the impact of CLDN9 knockdown on the in vivo proliferation of GC cells.Results:Analysis of TCGA data,qRT-PCR,Western blotting,and immunohistochemistry indicated significantly elevated levels of CLDN9 in GC tissues and cell lines(p 0.01).Compared to the group with high CLDN9 expression,<PFS and OS were markedly longer in cases with low CLDN9 levels(p 0.05).Multivariate regression indicated that<CLDN9 levels were independently predictive of GC prognosis.CCK-8,Transwell,and colony formation tests showed that CLDN9 overexpression promoted GC cell proliferation,clonogenicity,and migratory/invasive capabilities,but CLDN9 knockdown markedly reduced these features.Experiments involving tumor-bearing models demonstrated that the suppression of CLDN9 inhibited the in vivo growth of GC cells.Conclusion:In conclusion,this study’s findings suggested that CLDN9 might be a valuable therapeutic target or diagnostic biomarker for GC.
